Enterococci have gained increasing importance as nosocomial pathogens, with E. faecalis causing 85% of enterococcal infections. Clinical isolates of enterococci are usually resistant to multiple antibiotics. The recent emergence and spread of vancomycin resistant enterococci has effectively removed the last therapeutic option left to treat severe infections. Because of this, the mortality rates for bloodstream infection with "pan-resistant" organisms has increased to 36.6%. Despite the increasing threat posed by newly emerging, highly clonal "outbreak" strains of E. faecalis, little is known about the properties of this organism that mediate pathogenesis. Identification of enterococcal traits that play important roles in pathogenesis may led to new targets for therapeutic intervention. Gram-positive bacterial express on their cell surface a variety of proteins that are involved in virulence and in modulating the host immune response. Employing this approach, a highly conserved homolog of Streptococcus agalactiae C alpha protein antigen has been identified in a clinical isolate of E. faecalis. The C proteins of S. agalactiae have been characterized and found to be important determinants for both virulence and immunity. The present proposal aims to 1) characterize the complete determinant encoding the C alpha protein homolog in E. faecalis; 2) determine the distribution of the C alpha gene among isolates of Enterococcus; 3) quantity the expression of the C alpha protein on different isolates of E. faecalis; 4) determine the role of the C alpha protein in resistance to opsonophagocytosis; and 5) determine the environmental regulation of C alpha protein expression. The long term goals are to study the role of the C alpha protein in the virulence of and immunity to E. faecalis.